VPA985 IN HYPONATREMIA DUE TO INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

抗利尿激素血管加压素（AVP）是一种多肽激素，通过刺激特定的膜结合受体积极参与体液渗透压、血容量、血压和细胞增殖的调节，这些受体分为v1 -血管、v2 -肾脏和v3 -垂体亚型，具有不同的药理特征和细胞内第二信使。尿崩症的人类和实验模型表明，AVP的分泌是维持体液平衡的绝对需要。在与水和盐潴留有关的情况下，利钠剂的有用性已得到证实。然而，有些疾病（充血性心力衰竭的低钠血症、肝硬化、肾病综合征和抗利尿激素分泌不当综合征，SIADH）由于抗利尿激素释放不当而以过量潴留为特征。在这些情况下，通过产生游离水利尿而增加尿量的药物将具有显著的优势。本研究旨在评估单次口服VPA-985对SIADH所致低钠血症患者的疗效、安全性和耐受性。此外，初步的药代动力学和药效学参数将进行评估。这项研究刚刚开始招募患者。4 - 6名年龄在18 - 75岁之间的SIADH患者将被纳入该研究。招聘一直很困难。

Vasopressin (AVP), the antidiuretic hormone is a peptide hormone actively involved in the regulation of body fluid osmolality, blood volume, blood pressure, and cell proliferation via the stimulation of specific membrane-bound receptors classified into V1a-vascular, V2-renal, and V3-pituitary subtypes having distinct pharmacological profiles and intracellular second messengers. The secretion of AVP is an absolute requirement for the maintenance of fluid homeostasis as shown in human and experimental models of diabetes insipidus. The usefulness of natriuretic agents has been demonstrated in conditions associated with water and salt retention. However, there are diseases (hyponatremia of congestive heart failure, liver cirrhosis, nephrotic syndrome, and the syndrome of inappropriate secretion of antidiuretic hormone, SIADH) due to the inappropriate release of vasopressin and characterized by an excess retention of water. An agent that increases urine output by producing a free water diuresis would be of significant advantage in these conditions. This study is designed to evaluate the efficacy, safety, and tolerance of a single oral dose of VPA-985 in patients with hyponatremia due to SIADH. In addition, preliminary pharmacokinetic and pharmacodynamic parameters will be assessed. This study has just begun patient recruitment. Four to six patients with diagnosed SIADH between the ages of 18 and 75 years will be enrolled at this site. Recruitment has been difficult.